The long term goal of the Blood and Marrow Transplant Clinical Trial Network (BMT CTN) is to generate efficacy and safety data from multicenter Phase II and III trials, and advance the science and technology of immune and hematopoietic cellular therapies for the cure of blood disorders. The Moffitt Cancer Center has in place all the infrastructures for promoting and delivering immune and hematopoietic cellular therapies, with a robust Immunology Working Group properly positioned to design solutions, a GMP-compliant Cellular Therapy Facility for cell manufacturing and quality control, the BMT and the Immune and Cellular Therapy services to deliver established and experimental cellular therapies to patients with nonmalignant blood disorders, hematological malignancies and solid tumors. Our team is eager to contributing moving the field forward by collaborating with the BMT CTN for all the development steps of innovative cellular therapies. Specific Aim 1 is to collaborate with the BMT CTN in the design and conduct of multicenter studies and the dissemination of the results. Novel ideas start from teams of investigators at a single center, but significant advances in medical care require multicenter phase III randomized trials. Our team brings expertise in cellular immunotherapy, GVHD immunobiology, and behavioral studies. Moffitt Cancer Center has a fully established clinical and translational research program with a growing infrastructure to facilitate over 40 cellular therapy treatments and over 400 HSCT per year, and will continue to make BMT CTN trials available to patients in our institution. We bring unique science, clinical trial design experience, clinical expertise and volume, and our commitment to aggressively pursue these advances through the highly valuable BMT CTN network. Specific Aim 2 is to test the efficacy of ustekinumab for GVHD prophylaxis in a phase III multicenter trial by the BMT CTN. The BMT research program has recognized that Th17 are important effectors in GVHD alongside Th1 cells both in rodents and human transplants, and that the p40 subunit shared with IL-12 and IL-23 is relevant to GVHD pathogenesis. We present preliminary data from a placebo-controlled proof-of-principle clinical trial that ustekinumab (StelaraTM), an antibody against the human p40, polarizes T cells to Th2 while dampening Th1 and Th17 after allogenic HSCT. The clinical data also suggest that ustekinumab has the potential for mitigating both acute and chronic GVHD, and improving survival without disrupting graft-vs-leukemia responses. Our proposed concept for a definitive multicenter trial addresses the significant unmet need to prevent acute and chronic GVHD, and positive results will exert a sustained, powerful influence on the future clinical research in GVHD prevention and expand utilization of allogeneic HSCT.